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Lung Surfactant Protein B Peptide Mimics Interact with the Human ACE2 Receptor

Lung surfactant is a complex mixture of phospholipids and surfactant proteins that is produced in alveolar type 2 cells. It prevents lung collapse by reducing surface tension and is involved in innate immunity. Exogenous animal-derived and, more recently, synthetic lung surfactant has shown clinical...

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Autores principales: Waring, Alan J., Jung, Grace C.-L., Sharma, Shantanu K., Walther, Frans J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341807/
https://www.ncbi.nlm.nih.gov/pubmed/37446012
http://dx.doi.org/10.3390/ijms241310837
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author Waring, Alan J.
Jung, Grace C.-L.
Sharma, Shantanu K.
Walther, Frans J.
author_facet Waring, Alan J.
Jung, Grace C.-L.
Sharma, Shantanu K.
Walther, Frans J.
author_sort Waring, Alan J.
collection PubMed
description Lung surfactant is a complex mixture of phospholipids and surfactant proteins that is produced in alveolar type 2 cells. It prevents lung collapse by reducing surface tension and is involved in innate immunity. Exogenous animal-derived and, more recently, synthetic lung surfactant has shown clinical efficacy in surfactant-deficient premature infants and in critically ill patients with acute respiratory distress syndrome (ARDS), such as those with severe COVID-19 disease. COVID-19 pneumonia is initiated by the binding of the viral receptor-binding domain (RBD) of SARS-CoV-2 to the cellular receptor angiotensin-converting enzyme 2 (ACE2). Inflammation and tissue damage then lead to loss and dysfunction of surface activity that can be relieved by treatment with an exogenous lung surfactant. Surfactant protein B (SP-B) is pivotal for surfactant activity and has anti-inflammatory effects. Here, we study the binding of two synthetic SP-B peptide mimics, Super Mini-B (SMB) and B-YL, to a recombinant human ACE2 receptor protein construct using molecular docking and surface plasmon resonance (SPR) to evaluate their potential as antiviral drugs. The SPR measurements confirmed that both the SMB and B-YL peptides bind to the rhACE2 receptor with affinities like that of the viral RBD–ACE2 complex. These findings suggest that synthetic lung surfactant peptide mimics can act as competitive inhibitors of the binding of viral RBD to the ACE2 receptor.
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spelling pubmed-103418072023-07-14 Lung Surfactant Protein B Peptide Mimics Interact with the Human ACE2 Receptor Waring, Alan J. Jung, Grace C.-L. Sharma, Shantanu K. Walther, Frans J. Int J Mol Sci Article Lung surfactant is a complex mixture of phospholipids and surfactant proteins that is produced in alveolar type 2 cells. It prevents lung collapse by reducing surface tension and is involved in innate immunity. Exogenous animal-derived and, more recently, synthetic lung surfactant has shown clinical efficacy in surfactant-deficient premature infants and in critically ill patients with acute respiratory distress syndrome (ARDS), such as those with severe COVID-19 disease. COVID-19 pneumonia is initiated by the binding of the viral receptor-binding domain (RBD) of SARS-CoV-2 to the cellular receptor angiotensin-converting enzyme 2 (ACE2). Inflammation and tissue damage then lead to loss and dysfunction of surface activity that can be relieved by treatment with an exogenous lung surfactant. Surfactant protein B (SP-B) is pivotal for surfactant activity and has anti-inflammatory effects. Here, we study the binding of two synthetic SP-B peptide mimics, Super Mini-B (SMB) and B-YL, to a recombinant human ACE2 receptor protein construct using molecular docking and surface plasmon resonance (SPR) to evaluate their potential as antiviral drugs. The SPR measurements confirmed that both the SMB and B-YL peptides bind to the rhACE2 receptor with affinities like that of the viral RBD–ACE2 complex. These findings suggest that synthetic lung surfactant peptide mimics can act as competitive inhibitors of the binding of viral RBD to the ACE2 receptor. MDPI 2023-06-29 /pmc/articles/PMC10341807/ /pubmed/37446012 http://dx.doi.org/10.3390/ijms241310837 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Waring, Alan J.
Jung, Grace C.-L.
Sharma, Shantanu K.
Walther, Frans J.
Lung Surfactant Protein B Peptide Mimics Interact with the Human ACE2 Receptor
title Lung Surfactant Protein B Peptide Mimics Interact with the Human ACE2 Receptor
title_full Lung Surfactant Protein B Peptide Mimics Interact with the Human ACE2 Receptor
title_fullStr Lung Surfactant Protein B Peptide Mimics Interact with the Human ACE2 Receptor
title_full_unstemmed Lung Surfactant Protein B Peptide Mimics Interact with the Human ACE2 Receptor
title_short Lung Surfactant Protein B Peptide Mimics Interact with the Human ACE2 Receptor
title_sort lung surfactant protein b peptide mimics interact with the human ace2 receptor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341807/
https://www.ncbi.nlm.nih.gov/pubmed/37446012
http://dx.doi.org/10.3390/ijms241310837
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